Abstract The intense efforts for proteomics and biomarker discovery carried out by major research consortia such as EDRN (Early Detection Research Network) have generated many biomarkers, including those that are FDA-approved. However the transfer of biomarker detection and screening from research to clinical has been unsuccessful. The nanoLC-MS technique used in proteomic biomarker discovery is wrought with the inherent fragility and variability of the components of the experimental set-up. The weakest link in this transfer process is the fused silica spray emitter and columns which are easily clogged and damaged, and dead-volume must be painstaking eliminated because of the low flow-rate of sub- microliter/min to minimize peak broadening. Phoenix S&T has discovered patent-pending and patented metallic and plastic spray emitters with reduced surface interactions with the aqueous component of the buffer such that the cone-jet mode spray with high ion production efficiency are consistently and robustly produced at flow-rates from sub-microliter/min up to >100 uL/min. No fragile equipment is needed for use with these emitters. At flow-rates of a few microliters/min, the dead-volume elimination requirement is relaxed. The sensitivity obtained with these emitters at flow-rates less than 10 uL/min has been shown to be comparable to or exceeding that obtained with nanoLC-MS. These attributes offered by the new spray emitters make the transfer of the methods for biomarker screening into the clinics for medical decision making much more feasible. The proposed research aims to characterize these emitters to optimize the performance and durability of the emitters and enable reproducible manufacturing, and also to create plastic spray emitters with the potential of having the additional benefits of a ?softer? ionization that reduces in-source fragmentation and being disposable when used with dirty clinical samples. The learning? from the proposed research on these emitters may also open up possibility of 2D electrospray-MS devices for high throughput analyses of cellular functions in the future.